Project Summary Genomic investigation has shown that the ATP1A3 gene has a very high intolerance of mutation. This is emerging clinically as a rapidly expanding spectrum of neurological and psychiatric disease. Several syndromes have been identified with a wide range of severity. These include severe infantile epilepsy; severe infantile hypotonia; alternating hemiplegia of childhood (AHC); rapid-onset dystonia-parkinsonism (RDP); relapsing encephalopathy with cerebellar ataxia (RECA); cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorimotor deafness (CAPOS); and early onset schizophrenia. Despite several distinct groups of mutations, many specific neurological symptoms as well as developmental delay appear on a continuum. Age of onset also has a wide range from birth to adulthood. Available treatments are minimal, not based on disease mechanism, and simply inadequate. On the positive side, the ATP1A3 encoded protein alpha 3 is a virtually neuron-specific isoform of Na,K-ATPase, and there is a substantial body of scientific knowledge related to its physiology and mechanism. This results in a very credible opportunity for cross-disciplinary interactions that could lead to effective therapies. A highly-interactive body of clinicians, geneticists, basic scientists, patient advocacy leaders, and parents of patients have met annually since 2012. This application is for funding for the 7th annual meeting, to be held in Chicago in 2018. The interdisciplinary format and the full participation of committed family members and advocates has produced very important insights and education at all levels. Consensus developments have shaped subsequent clinical and basic research, and forged new collaborations. Research topics discussed include new phenotypes; novel genetics; treatments of animal models; stem cell and cell model investigations; biochemical studies of mutations and phenotype correlations; planned clinical trials; clinical data repositories; and ideas for new treatments. The selection of a different geographical location for each meeting has facilitated the participation of local clinicians and parents. The meetings have been an outstanding learning environment for young investigators and clinical fellows that will continue in Chicago 2018.